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脂多糖诱导新生小鼠巨细胞病毒感染性迷路炎:先天性巨细胞病毒感染致听力损失的模型

Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection.

作者信息

Li Li, Kosugi Isao, Han Gui-Ping, Kawasaki Hideya, Arai Yoshifumi, Takeshita Tamotsu, Tsutsui Yoshihiro

机构信息

Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

Lab Invest. 2008 Jul;88(7):722-30. doi: 10.1038/labinvest.2008.39. Epub 2008 May 12.

Abstract

Congenital cytomegalovirus (CMV) infection is the most common infectious cause of sensorineural hearing loss in children. Here, we established an experimental model of hearing loss after systemic infection with murine CMV (MCMV) in newborn mice. Although almost no viral infection was observed in the inner ears and brains by intraperitoneal (i.p.) infection with MCMV in newborn mice, infection in these regions was induced in combination with intracerebral (i.c.) injection of bacterial lipopolysaccharide (LPS). The susceptibility of the inner ears was higher than that of the brains in terms of viral titer per unit weight. In the labyrinths, the viral infection was associated with the mesenchymal vessels and accompanied by inflammatory cells induced by LPS, causing hematogenous targets of infection in the labyrinths. Viral infection also spread in the perilymph regions such as the scala tympani and scala vestibuli, probably from infected brains via meningogenic and cochlear nerve routes. Viral infection was not observed in the scala media in the endolymph, including the Corti organ. However, viral infection was observed in the spiral limbus, including the stria vascularis. These results suggest that hearing loss caused by labyrinthitis after congenital CMV infection may be enhanced by inflammation caused by systemic bacterial infection in the neonatal period.

摘要

先天性巨细胞病毒(CMV)感染是儿童感音神经性听力损失最常见的感染原因。在此,我们建立了新生小鼠经鼠巨细胞病毒(MCMV)全身感染后听力损失的实验模型。尽管新生小鼠经腹腔注射MCMV后在内耳和大脑中几乎未观察到病毒感染,但联合脑内注射细菌脂多糖(LPS)可诱导这些区域的感染。就每单位重量的病毒滴度而言,内耳的易感性高于大脑。在迷宫中,病毒感染与间充质血管相关,并伴有LPS诱导的炎性细胞,导致迷宫中的血源性感染靶点。病毒感染还可能从受感染的大脑通过脑膜源性和耳蜗神经途径扩散到外淋巴区域,如鼓阶和前庭阶。在内淋巴中的中阶,包括柯蒂氏器,未观察到病毒感染。然而,在包括血管纹在内的螺旋缘中观察到了病毒感染。这些结果表明,先天性CMV感染后迷路炎导致的听力损失可能因新生儿期全身细菌感染引起的炎症而加重。

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